Density and sub-cellular distribution of cardiac and neuronal sodium channel isoforms in rat ventricular myocytes
Density and sub-cellular distribution of cardiac and neuronal sodium channel isoforms in rat ventricular myocytes
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DOI：
10.1016/j.bbrc.2006.07.189
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发表时间：
2006-09-29
影响因子：
3.1
通讯作者：
Orchard, Clive H.
中科院分区：
文献类型：
--
作者：
Brette, Fabien;Orchard, Clive H.
在心室肌细胞中，Na电流主要由心脏Na（V）1.5亚型产生，但最近已证实心脏中存在“神经元”Na通道亚型。在这项研究中，我们定量的密度和亚细胞分布的心脏和神经元通道亚型在大鼠心室肌细胞。用膜片钳技术记录对照组和去微管组心肌细胞的I-Na。去微管减少了细胞电容（类似于29%），但最大电导没有改变（1.94 +/- 0.15，14个对照组vs 1.98 +/- 0.19 nS/pF，17个去微管肌细胞）。I-Na的动力学性质在两种细胞类型中相似，表明表面和t-小管膜的良好电压控制。假设我们最近提供的亚细胞电流定位，我们计算了Na通道密度（神经元亚型：类似于总肌膜电流的11%，类似于细胞表面的3%，类似于t-小管电流的31%）。考虑到使用低Na浓度后，假定心脏和神经元亚型的单通道电导分别为2.2和2.5 pS。我们计算出心脏Na通道亚型的密度相对恒定（以通道/μ m（2）计：在总肌膜中类似于11，在细胞表面类似于13，在t-小管类似于10）。相比之下，神经元Na通道亚型集中在t-小管（通道/μ m（2）：与总肌层中的1相似，与细胞表面的0.3相似，与t-小管中的2.5相似）。我们的结论是，与骨骼肌中细胞表面的Na通道密度高于t-小管相反，心室心肌细胞中Na通道密度的亚细胞分布相对均匀（类似于13个通道/μ m（2））。(c)2006年爱思唯尔公司All rights reserved.
In cardiac ventricular myocytes, Na current is generated mainly by the cardiac Na(V)1.5 isoform, but the presence of "neuronal" Na channel isoforms in the heart has been demonstrated recently. In this study, we quantified the density and sub-cellular distribution of cardiac and neuronal channel isoforms in rat ventricular myocytes. I-Na was recorded using the patch clamp technique in control and detubulated myocytes. Detubulation reduced cell capacitance (by similar to 29%) but maximum conductance was not altered (1.94 +/- 0.15, 14 control vs 1.98 +/- 0.19 nS/pF, 17 detubulated myocytes). The kinetic properties of I-Na were similar in both cell types suggesting good voltage control of surface and t-tubule membranes. We calculated Na channel densities assuming the sub-cellular current localization we recently provided (neuronal isoform: similar to 11% of total sarcolemmal current, similar to 3% of cell surface, and similar to 31% of t-tubule current). Single channel conductances were assumed to be 2.2 and 2.5 pS for the cardiac and neuronal isoforms, respectively, after accounting for the use of low Na concentration. We calculated that the density of the cardiac Na channel isoform is relatively constant (in channels/mu m(2) : similar to 11 in total sarcolemma, similar to 13 at the cell surface, similar to 10 at the t-tubules). In contrast, neuronal Na channel isoforms are concentrated at the t-tubules (in channels/mu m(2) : similar to 1 in total sarcolernma, similar to 0.3 at the cell surface, similar to 2.5 at the t-tubules). We conclude that, in contrast to skeletal muscle in which Na channel density is higher at the cell surface than the t-tubules, in ventricular cardiac myocytes the sub-cellular distribution of Na channel density is relatively homogeneous (similar to 13 channels/mu m(2)). (c) 2006 Elsevier Inc. All rights reserved.